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P43136

- NR2F6_MOUSE

UniProt

P43136 - NR2F6_MOUSE

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Protein

Nuclear receptor subfamily 2 group F member 6

Gene

Nr2f6

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin-choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine-dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4+ T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC).3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi54 – 12976Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri57 – 7721NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri93 – 11725NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Source: InterPro
  2. RNA polymerase II distal enhancer sequence-specific DNA binding Source: NTNU_SB
  3. RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: NTNU_SB
  4. steroid hormone receptor activity Source: InterPro
  5. zinc ion binding Source: InterPro

GO - Biological processi

  1. detection of temperature stimulus involved in sensory perception of pain Source: MGI
  2. entrainment of circadian clock by photoperiod Source: MGI
  3. negative regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  4. neuron development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Receptor, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_234105. Nuclear Receptor transcription pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor subfamily 2 group F member 6
Alternative name(s):
COUP transcription factor 3
Short name:
COUP-TF3
V-erbA-related protein 2
Short name:
EAR-2
Gene namesi
Name:Nr2f6
Synonyms:Ear-2, Ear2, Erbal2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 8

Organism-specific databases

MGIiMGI:1352453. Nr2f6.

Subcellular locationi

Nucleus 1 PublicationPROSITE-ProRule annotation

GO - Cellular componenti

  1. nucleus Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Reduction of neurons in the locus coerulus of the developing cortex. Defects in circadian behavior. Hyperreactive lymphocytes, late-onset immunopathology and hypersusceptibility to Th17-dependent experimental autoimmune encephalomyelitis.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 390390Nuclear receptor subfamily 2 group F member 6PRO_0000053614Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei41 – 411PhosphoserineBy similarity
Modified residuei84 – 841PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP43136.
PaxDbiP43136.
PRIDEiP43136.

PTM databases

PhosphoSiteiP43136.

Expressioni

Developmental stagei

Initially expressed at E8.5 in the developing rhombencephalon. At E11.5 expression in the CNS rapidly decreases and in newborn and adult expression is not detectable in the brain with the exceptions of Purkinje neurons and the choroid plexi.1 Publication

Gene expression databases

BgeeiP43136.
CleanExiMM_NR2F6.
ExpressionAtlasiP43136. baseline and differential.
GenevestigatoriP43136.

Interactioni

Subunit structurei

Binds DNA as dimer; homodimer and heterodimer with NR2F2 and probably NR2F1. Interacts with THRB (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Rasd1O356265EBI-4319956,EBI-4319979

Protein-protein interaction databases

BioGridi199494. 4 interactions.
IntActiP43136. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliP43136.
SMRiP43136. Positions 55-384.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni163 – 390228Ligand-bindingBy similarityAdd
BLAST
Regioni314 – 39077Important for dimerizationBy similarityAdd
BLAST

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri57 – 7721NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri93 – 11725NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG277317.
GeneTreeiENSGT00760000118948.
HOGENOMiHOG000260820.
HOVERGENiHBG005606.
InParanoidiP43136.
KOiK08549.
OMAiSDMEAGD.
OrthoDBiEOG72RMZ5.
TreeFamiTF352097.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR003068. COUP_TF.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01282. COUPTNFACTOR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P43136-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAMVTGGWGD PGGDTNGVDK AGGSYPRATE DDSASPPGAT SDAEPGDEER
60 70 80 90 100
PGLQVDCVVC GDKSSGKHYG VFTCEGCKSF FKRSIRRNLS YTCRSNRDCQ
110 120 130 140 150
IDQHHRNQCQ YCRLKKCFRV GMRKEAVQRG RIPHALPGPA ACSPPGATGV
160 170 180 190 200
EPFTGPPVSE LIAQLLRAEP YPAAGRFGGG GAVLGIDNVC ELAARLLFST
210 220 230 240 250
VEWARHAPFF PELPAADQVA LLRLSWSELF VLNAAQAALP LHTAPLLAAA
260 270 280 290 300
GLHAAPMAAE RAVAFMDQVR AFQEQVDKLG RLQVDAAEYG CLKAIALFTP
310 320 330 340 350
DACGLSDPAH VESLQEKAQV ALTEYVRAQY PSQPQRFGRL LLRLPALRAV
360 370 380 390
PASLISQLFF MRLVGKTPIE TLIRDMLLSG STFNWPYGSG
Length:390
Mass (Da):41,968
Last modified:July 27, 2011 - v2
Checksum:i4C30B25C6CAE5338
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti10 – 101D → G in AAA37532. (PubMed:8194772)Curated
Sequence conflicti84 – 841S → T in CAA54097. (PubMed:7947324)Curated
Sequence conflicti84 – 841S → T in AAA37532. (PubMed:8194772)Curated
Sequence conflicti152 – 1521P → H in AAA37532. (PubMed:8194772)Curated
Sequence conflicti164 – 1652QL → HV in AAA37532. (PubMed:8194772)Curated
Sequence conflicti196 – 1983LLF → AV in AAA37532. (PubMed:8194772)Curated
Sequence conflicti239 – 2413LPL → VAV in AAA37532. (PubMed:8194772)Curated
Sequence conflicti357 – 3571Q → K in CAA54097. (PubMed:7947324)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X76654 mRNA. Translation: CAA54097.1.
L25674 mRNA. Translation: AAA37532.1.
AK131941 mRNA. Translation: BAE20887.1.
AK171552 mRNA. Translation: BAE42523.1.
CH466569 Genomic DNA. Translation: EDL28911.1.
BC008138 mRNA. Translation: AAH08138.1.
CCDSiCCDS22392.1.
PIRiI48734. S44285.
I49640.
RefSeqiNP_034280.2. NM_010150.2.
UniGeneiMm.28989.
Mm.440170.

Genome annotation databases

EnsembliENSMUST00000002466; ENSMUSP00000002466; ENSMUSG00000002393.
GeneIDi13864.
KEGGimmu:13864.
UCSCiuc009mcx.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X76654 mRNA. Translation: CAA54097.1 .
L25674 mRNA. Translation: AAA37532.1 .
AK131941 mRNA. Translation: BAE20887.1 .
AK171552 mRNA. Translation: BAE42523.1 .
CH466569 Genomic DNA. Translation: EDL28911.1 .
BC008138 mRNA. Translation: AAH08138.1 .
CCDSi CCDS22392.1.
PIRi I48734. S44285.
I49640.
RefSeqi NP_034280.2. NM_010150.2.
UniGenei Mm.28989.
Mm.440170.

3D structure databases

ProteinModelPortali P43136.
SMRi P43136. Positions 55-384.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 199494. 4 interactions.
IntActi P43136. 1 interaction.

PTM databases

PhosphoSitei P43136.

Proteomic databases

MaxQBi P43136.
PaxDbi P43136.
PRIDEi P43136.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000002466 ; ENSMUSP00000002466 ; ENSMUSG00000002393 .
GeneIDi 13864.
KEGGi mmu:13864.
UCSCi uc009mcx.1. mouse.

Organism-specific databases

CTDi 2063.
MGIi MGI:1352453. Nr2f6.

Phylogenomic databases

eggNOGi NOG277317.
GeneTreei ENSGT00760000118948.
HOGENOMi HOG000260820.
HOVERGENi HBG005606.
InParanoidi P43136.
KOi K08549.
OMAi SDMEAGD.
OrthoDBi EOG72RMZ5.
TreeFami TF352097.

Enzyme and pathway databases

Reactomei REACT_234105. Nuclear Receptor transcription pathway.

Miscellaneous databases

NextBioi 284756.
PROi P43136.
SOURCEi Search...

Gene expression databases

Bgeei P43136.
CleanExi MM_NR2F6.
ExpressionAtlasi P43136. baseline and differential.
Genevestigatori P43136.

Family and domain databases

Gene3Di 1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProi IPR003068. COUP_TF.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view ]
Pfami PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view ]
PRINTSi PR01282. COUPTNFACTOR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTi SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view ]
SUPFAMi SSF48508. SSF48508. 1 hit.
PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and expression during development of three murine members of the COUP family of nuclear orphan receptors."
    Jonk L.J.C., de Jonge M.E.J., Pals C.E.G.M., Wissink S., Vervaart J.M.A., Schoorlemmer J., Kruijer W.
    Mech. Dev. 47:81-97(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The sequence of a murine cDNA encoding Ear-2, a nuclear orphan receptor."
    Barnhart K.M., Mellon P.L.
    Gene 142:313-314(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Pituitary.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Mammary tumor.
  6. "Heterodimeric interactions between chicken ovalbumin upstream promoter-transcription factor family members ARP1 and ear2."
    Avram D., Ishmael J.E., Nevrivy D.J., Peterson V.J., Lee S.H., Dowell P., Leid M.
    J. Biol. Chem. 274:14331-14336(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, INTERACTION WITH NR2F2.
  7. "Friend of GATA 2 physically interacts with chicken ovalbumin upstream promoter-TF2 (COUP-TF2) and COUP-TF3 and represses COUP-TF2-dependent activation of the atrial natriuretic factor promoter."
    Huggins G.S., Bacani C.J., Boltax J., Aikawa R., Leiden J.M.
    J. Biol. Chem. 276:28029-28036(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ZFPM2.
  8. "Identification of a nuclear orphan receptor (Ear2) as a negative regulator of renin gene transcription."
    Liu X., Huang X., Sigmund C.D.
    Circ. Res. 92:1033-1040(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DNA-BINDING, SUBCELLULAR LOCATION.
  9. "Abnormal development of the locus coeruleus in Ear2(Nr2f6)-deficient mice impairs the functionality of the forebrain clock and affects nociception."
    Warnecke M., Oster H., Revelli J.P., Alvarez-Bolado G., Eichele G.
    Genes Dev. 19:614-625(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
  10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  11. "The nuclear orphan receptor NR2F6 suppresses lymphocyte activation and T helper 17-dependent autoimmunity."
    Hermann-Kleiter N., Gruber T., Lutz-Nicoladoni C., Thuille N., Fresser F., Labi V., Schiefermeier N., Warnecke M., Huber L., Villunger A., Eichele G., Kaminski S., Baier G.
    Immunity 29:205-216(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiNR2F6_MOUSE
AccessioniPrimary (citable) accession number: P43136
Secondary accession number(s): Q61504, Q922G8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: July 27, 2011
Last modified: November 26, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3